CN1177848C - 可用作lh激动剂的二环杂芳族化合物 - Google Patents

可用作lh激动剂的二环杂芳族化合物 Download PDF

Info

Publication number
CN1177848C
CN1177848C CNB008069077A CN00806907A CN1177848C CN 1177848 C CN1177848 C CN 1177848C CN B008069077 A CNB008069077 A CN B008069077A CN 00806907 A CN00806907 A CN 00806907A CN 1177848 C CN1177848 C CN 1177848C
Authority
CN
China
Prior art keywords
amino
alkyl
aryl
carbonyl
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CNB008069077A
Other languages
English (en)
Chinese (zh)
Other versions
CN1349535A (zh
Inventor
G��G���Ϳ���
G·G·吉里特斯马
R
N·C·R·范斯特拉藤
P
A·E·P·阿丹
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme BV
Original Assignee
Akzo Nobel NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Akzo Nobel NV filed Critical Akzo Nobel NV
Publication of CN1349535A publication Critical patent/CN1349535A/zh
Application granted granted Critical
Publication of CN1177848C publication Critical patent/CN1177848C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/16—Masculine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Endocrinology (AREA)
  • Public Health (AREA)
  • Reproductive Health (AREA)
  • Diabetes (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
CNB008069077A 1999-04-08 2000-04-03 可用作lh激动剂的二环杂芳族化合物 Expired - Fee Related CN1177848C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP99201152.8 1999-04-08
EP99201152 1999-04-08

Publications (2)

Publication Number Publication Date
CN1349535A CN1349535A (zh) 2002-05-15
CN1177848C true CN1177848C (zh) 2004-12-01

Family

ID=8240094

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB008069077A Expired - Fee Related CN1177848C (zh) 1999-04-08 2000-04-03 可用作lh激动剂的二环杂芳族化合物

Country Status (30)

Country Link
US (2) US6569863B1 (pl)
EP (1) EP1171443B1 (pl)
JP (1) JP4854856B2 (pl)
KR (1) KR100691546B1 (pl)
CN (1) CN1177848C (pl)
AR (1) AR028474A1 (pl)
AT (1) ATE299507T1 (pl)
AU (1) AU772258B2 (pl)
BR (1) BRPI0009558B1 (pl)
CA (1) CA2368834C (pl)
CO (1) CO5160348A1 (pl)
CZ (1) CZ300832B6 (pl)
DE (1) DE60021262T2 (pl)
DK (1) DK1171443T3 (pl)
ES (1) ES2245304T3 (pl)
HK (1) HK1041266B (pl)
HU (1) HU229002B1 (pl)
ID (1) ID30502A (pl)
IL (2) IL145483A0 (pl)
MX (1) MXPA01010144A (pl)
NO (1) NO328826B1 (pl)
NZ (1) NZ514445A (pl)
PE (1) PE20010030A1 (pl)
PL (1) PL219316B1 (pl)
PT (1) PT1171443E (pl)
RU (1) RU2248979C2 (pl)
TR (1) TR200102839T2 (pl)
TW (1) TW564247B (pl)
WO (1) WO2000061586A1 (pl)
ZA (1) ZA200107917B (pl)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002213929B2 (en) * 2000-09-22 2006-04-13 Merck Sharp & Dohme B.V. Bicyclic heteroaromatic compounds
GB0100622D0 (en) 2001-01-10 2001-02-21 Vernalis Res Ltd Chemical compounds V111
DE10108481A1 (de) 2001-02-22 2002-10-24 Bayer Ag Pyridylpyrimidine
TWI228508B (en) * 2001-09-04 2005-03-01 Akzo Nobel Nv Thieno[2,3-d]pyrimidines with combined LH and FSH agonistic activity
NZ531375A (en) * 2001-09-04 2005-06-24 Akzo Nobel Nv Glycine-substituted thieno [2,3-d]pyrimidines with combined LH and FSH agonistic activity may be used to treat fertility disorders
US6974870B2 (en) 2002-06-06 2005-12-13 Boehringer Ingelheim Phamaceuticals, Inc. Substituted 3-amino-thieno [2,3-b]pyridine-2-carboxylic acid amide compounds and processes for preparing and their uses
EP1513516B1 (en) 2002-06-06 2008-12-03 Boehringer Ingelheim Pharmaceuticals Inc. SUBSTITUTED 3-AMINO-THIENO(2,3-b) PYRIDINE-2-CARBOXYLIC ACID AMIDE COMPOUNDS AND PROCESSES FOR PREPARING AND THEIR USES
US7674791B2 (en) 2003-04-09 2010-03-09 Biogen Idec Ma Inc. Triazolopyrazines and methods of making and using the same
WO2004092170A2 (en) 2003-04-09 2004-10-28 Biogen Idec Ma Inc. Triazolotriazines and pyrazolotriazines useful as a2a adenosine receptor antagon ists
EP1633756B1 (en) 2003-04-09 2008-12-24 Biogen Idec MA Inc. A2a adenosine receptor antagonists
JPWO2005019225A1 (ja) * 2003-08-21 2007-11-01 杏林製薬株式会社 Ｎｋ１受容体拮抗作用を有する化合物の製造方法及びその製造中間体
US7550485B2 (en) * 2003-10-14 2009-06-23 Wyeth Substituted N-heterocycle derivatives and methods of their use
AU2004283751B2 (en) * 2003-10-24 2011-05-19 Exelixis, Inc. p70S6 kinase modulators and method of use
US7781478B2 (en) 2004-07-14 2010-08-24 Ptc Therapeutics, Inc. Methods for treating hepatitis C
JP2008507518A (ja) * 2004-07-22 2008-03-13 ピーティーシー セラピューティクス，インコーポレーテッド Ｃ型肝炎を治療するためのチエノピリジン
WO2007062222A2 (en) * 2005-11-22 2007-05-31 University Of South Florida Inhibition of cell proliferation
TWI417095B (zh) 2006-03-15 2013-12-01 Janssen Pharmaceuticals Inc １，４-二取代之３-氰基-吡啶酮衍生物及其作為ｍＧｌｕＲ２-受體之正向異位性調節劑之用途
CA2652061A1 (en) * 2006-05-17 2007-11-29 Marvin C. Gershengorn Pyrimidine low molecular weight ligands for modulating hormone receptors
WO2007146602A1 (en) 2006-06-06 2007-12-21 Boehringer Ingelheim International Gmbh Substituted 3-amino-thieno[2,3-b] pyridine-2-carboxamide compounds, their preparation and use
RU2444524C2 (ru) * 2006-08-21 2012-03-10 Дженентек, Инк. Азабензотиофенильные соединения и способы применения
TW200845978A (en) 2007-03-07 2008-12-01 Janssen Pharmaceutica Nv 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives
TW200900065A (en) 2007-03-07 2009-01-01 Janssen Pharmaceutica Nv 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives
US9114138B2 (en) 2007-09-14 2015-08-25 Janssen Pharmaceuticals, Inc. 1′,3′-disubstituted-4-phenyl-3,4,5,6-tetrahydro-2H,1′H-[1,4′] bipyridinyl-2′-ones
EA019085B1 (ru) 2007-09-14 2014-01-30 Янссен Фармасьютикалз, Инк. 1',3-двузамещенные 4-(арил-х-фенил)-1н-пиридин-2-оны
TW200927731A (en) * 2007-09-14 2009-07-01 Ortho Mcneil Janssen Pharm 1,3-disubstituted-4-phenyl-1H-pyridin-2-ones
CN101903394B (zh) * 2007-10-18 2013-12-25 贝林格尔.英格海姆国际有限公司 二氢噻吩并[3,2-d]嘧啶的制备及其中使用的中间体
JP5433582B2 (ja) 2007-11-14 2014-03-05 ジャンセン ファーマシューティカルズ， インコーポレイテッド． イミダゾ［１，２−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体の正のアロステリック調節因子としてのその使用
WO2010025890A1 (en) 2008-09-02 2010-03-11 Ortho-Mcneil-Janssen Pharmaceuticals, Inc 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors
AU2009304293B2 (en) 2008-10-16 2012-04-26 Addex Pharma S.A. Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors
AU2009319387B2 (en) 2008-11-28 2012-05-10 Addex Pharma S.A. Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors
JP5634506B2 (ja) 2009-05-12 2014-12-03 ジャンセン ファーマシューティカルズ， インコーポレイテッド １，２，３−トリアゾロ［４，３−ａ］ピリジン誘導体ならびに神経障害および精神障害の治療または予防のためのその使用
CA2760259C (en) 2009-05-12 2018-05-01 Janssen Pharmaceuticals, Inc. 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
MY153913A (en) 2009-05-12 2015-04-15 Janssen Pharmaceuticals Inc 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
JP5852665B2 (ja) 2010-11-08 2016-02-03 ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド １，２，４−トリアゾロ［４，３−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体のポジティブアロステリックモジュレーターとしてのそれらの使用
ES2552455T3 (es) 2010-11-08 2015-11-30 Janssen Pharmaceuticals, Inc. Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2
JP5852666B2 (ja) 2010-11-08 2016-02-03 ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド １，２，４−トリアゾロ［４，３−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体のポジティブアロステリックモジュレーターとしてのそれらの使用
JP2014520869A (ja) 2011-07-18 2014-08-25 アルツ バイオロジクス アクティーゼルスカブ 長期作用性で生物学的活性が有る黄体形成ホルモン（ｌｈ）化合物
CA2855446C (en) 2011-11-23 2021-04-20 Cancer Research Technology Limited Thienopyrimidine inhibitors of atypical protein kinase c
JO3368B1 (ar) 2013-06-04 2019-03-13 Janssen Pharmaceutica Nv مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2
JO3367B1 (ar) 2013-09-06 2019-03-13 Janssen Pharmaceutica Nv مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2
WO2015110435A1 (en) 2014-01-21 2015-07-30 Janssen Pharmaceutica Nv Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use
LT3096790T (lt) 2014-01-21 2019-10-10 Janssen Pharmaceutica, N.V. Deriniai, apimantys 2 potipio metabotropinio glutamaterginio receptoriaus teigiamus alosterinius moduliatorius arba ortosterinius agonistus, ir jų panaudojimas
CN107602585A (zh) * 2017-10-23 2018-01-19 遵义医学院 噻吩并吡啶双杂环化合物的制备工艺
BR102019022529A2 (pt) * 2019-10-25 2021-05-04 Anhanguera Educacional Ltda. Processo para obtenção de composições farmacêuticas antitumorais através de butadienos push-pull, compostos e seus usos

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993013664A2 (en) * 1992-01-11 1993-07-22 Schering Agrochemicals Limited Biheterocyclic fungicidal compounds
TW449600B (en) 1994-04-19 2001-08-11 Takeda Chemical Industries Ltd Condensed-ring thiophene derivatives, their production and use
JP3854648B2 (ja) * 1994-04-19 2006-12-06 武田薬品工業株式会社 縮合チオフェン誘導体、その製造法及び用途
CA2202985A1 (en) 1994-11-08 1996-05-17 Haruhiko Makino Thienopyridine or thienopyrimidine derivatives and their use
JPH09169767A (ja) * 1995-10-19 1997-06-30 Takeda Chem Ind Ltd 複素環化合物、その製造法および用途
JPH09169766A (ja) * 1995-10-19 1997-06-30 Takeda Chem Ind Ltd チエノピリジン誘導体，その製造法および用途
WO1997014697A1 (en) * 1995-10-19 1997-04-24 Takeda Chemical Industries, Ltd. Thienopyridine derivatives as gonadotropin releasing hormone antagonists
AU2406597A (en) 1996-04-26 1997-11-19 Takeda Chemical Industries Ltd. Thienopyridine derivatives, their production and use

Also Published As

Publication number Publication date
PL219316B1 (pl) 2015-04-30
PE20010030A1 (es) 2001-01-27
IL145483A0 (en) 2002-06-30
NO20014824L (no) 2001-10-04
CA2368834A1 (en) 2000-10-19
HU229002B1 (en) 2013-07-29
NO328826B1 (no) 2010-05-25
TW564247B (en) 2003-12-01
US6841553B2 (en) 2005-01-11
AR028474A1 (es) 2003-05-14
HUP0200653A3 (en) 2004-07-28
TR200102839T2 (tr) 2002-04-22
IL145483A (en) 2007-06-03
AU3816600A (en) 2000-11-14
AU772258B2 (en) 2004-04-22
JP4854856B2 (ja) 2012-01-18
PT1171443E (pt) 2005-11-30
KR20010103801A (ko) 2001-11-23
NO20014824D0 (no) 2001-10-04
DK1171443T3 (da) 2005-11-07
CN1349535A (zh) 2002-05-15
JP2002541259A (ja) 2002-12-03
WO2000061586A1 (en) 2000-10-19
HK1041266B (zh) 2005-09-16
DE60021262T2 (de) 2006-01-05
ES2245304T3 (es) 2006-01-01
BRPI0009558B1 (pt) 2016-10-25
ID30502A (id) 2001-12-13
CZ20013605A3 (cs) 2002-03-13
US6569863B1 (en) 2003-05-27
CO5160348A1 (es) 2002-05-30
MXPA01010144A (es) 2002-04-24
KR100691546B1 (ko) 2007-03-12
NZ514445A (en) 2003-07-25
HUP0200653A2 (en) 2002-06-29
RU2248979C2 (ru) 2005-03-27
ATE299507T1 (de) 2005-07-15
PL350964A1 (en) 2003-02-24
EP1171443B1 (en) 2005-07-13
DE60021262D1 (de) 2005-08-18
ZA200107917B (en) 2003-09-23
CA2368834C (en) 2009-11-03
CZ300832B6 (cs) 2009-08-19
HK1041266A1 (en) 2002-07-05
BR0009558A (pt) 2002-02-19
EP1171443A1 (en) 2002-01-16
US20030212081A1 (en) 2003-11-13

Similar Documents

Publication Publication Date Title
CN1177848C (zh) 可用作lh激动剂的二环杂芳族化合物
CN1065244C (zh) 三环苯并氮杂䓬加压素拮抗剂
CN1146566C (zh) 2-芳基-8-氧代二氢嘌呤衍生物及其制备方法、含该衍生物的药物组合物、及其中间体
CN1263756C (zh) 咪唑并嘧啶衍生物和***并嘧啶衍生物
CN1033088C (zh) 新的噻唑基苯并呋喃衍生物的制备方法
CN1171889C (zh) 作为p38蛋白激酶的抑制剂的杂烷基氨基－取代的双环氮杂环类化合物
CN1224623C (zh) 1－苯基磺酰基－1,3－二氢－2h－吲哚－2－酮衍生物,其制备及其治疗应用
CN1662236A (zh) 组蛋白脱乙酰基转移酶抑制剂
CN1275964C (zh) 作为细胞增殖抑制剂的7－氧代吡啶并嘧啶
CN1059142A (zh) 新的噻吩衍生物
CN1170827C (zh) 苯并呋喃基吡喃酮衍生物
CN1203069C (zh) 经取代的哌啶,含有这些化合物的药物组合物,及其制备方法
CN1489581A (zh) 喹唑啉酮衍生物
CN1173497A (zh) 含杂环碳酸衍生物
CN1111242A (zh) 苯磺酰胺衍生物及其制备方法
CN1057837A (zh) 取代的2-苯并[c]呋喃酮和杂环2-苯并[c]呋喃酮
CN1993359A (zh) 杂环取代的环状脲衍生物、其制备及其作为激酶抑制剂的药物用途
CN1549817A (zh) 作为半胱氨酸蛋白酶抑制剂的吡咯并嘧啶化合物
CN1204327A (zh) 药用活性喹唑啉类化合物
CN1522258A (zh) 新的4-氨基-5,6-取代的噻吩并[2,3-d]嘧啶化合物
CN1508137A (zh) 用作磷酸二酯酶抑制剂的2-苯基取代的咪唑并三嗪酮
CN1835746A (zh) 有丝***驱动蛋白抑制剂
CN1681804A (zh) 乙内酰脲衍生物以及用作tace抑制剂的用途
CN1835756A (zh) 有丝***驱动蛋白抑制剂
CN1106663A (zh) 噻吩并嘧啶衍生物及其制备方法和用途

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
ASS Succession or assignment of patent right

Owner name: ORGANON NV

Free format text: FORMER OWNER: AKZO NOVEL N.V. CORP.

Effective date: 20070105

C41 Transfer of patent application or patent right or utility model
TR01 Transfer of patent right

Effective date of registration: 20070105

Address after: Holland

Patentee after: N.V. ORGANON

Address before: Holland Arnhem

Patentee before: AKZO NOBEL N.V.

C56 Change in the name or address of the patentee

Owner name: MSD OS CO., LTD.

Free format text: FORMER NAME: ORGANON NV

CP01 Change in the name or title of a patent holder

Address after: Holland

Patentee after: N.V. Organon

Address before: Holland

Patentee before: N.V. ORGANON

ASS Succession or assignment of patent right

Owner name: ORGANON BIOLOGICAL NETHERLANDS CO., LTD.

Free format text: FORMER OWNER: MSD OUSI CO., LTD.

Effective date: 20131011

Owner name: MERCK SHARP + DOHME CORP.

Free format text: FORMER OWNER: ORGANON BIOLOGICAL NETHERLANDS CO., LTD.

Effective date: 20131011

C41 Transfer of patent application or patent right or utility model
TR01 Transfer of patent right

Effective date of registration: 20131011

Address after: Haarlem

Patentee after: MERCK SHARP & DOHME B.V.

Address before: Haarlem

Patentee before: Organon biological science Holland Co.,Ltd.

Effective date of registration: 20131011

Address after: Haarlem

Patentee after: Organon biological science Holland Co.,Ltd.

Address before: Holland

Patentee before: N.V. Organon

CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20041201

Termination date: 20180403